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Regulation of Sympathetic and Parasympathetic Activity
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Finally, the central role of the hypothalamus in the regulation of both sympathetic and parasympathetic activities must be emphasized This aspect of hypothalamic function is discussed in the preceding chapter (pages 456 and 466)
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The Pineal Gland and Melatonin
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The pineal gland, or pineal body, is a small glandular structure (about 9 mm in diameter) that projects from the dorsal dienceph-
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THE HYPOTHALAMUS AND NEUROENDOCRINE DISORDERS
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alon and lies just posterior to the third ventricle In the past the pineal body gured prominently in philosophic and religious writings; for Descartes it was the seat of the soul When this idea was discredited, the pineal gland was relegated to the status of a vestigial organ The identi cation of melatonin, the pineal hormone followed by recognition of its role in maintaining biologic rhythms and the modulating effects on its secretion by the circadian lightdark cycle revived scienti c interest in the structure Even though the hormone was found to have an indirect effect on several other neuroendocrine systems, neurologists took little interest in pineal function because ablation of the gland in humans, with attendant loss of most of the circulating melatonin, leads to few if any clinical changes It is the cyclic secretion of melatonin that appears to be the most important activity of the pineal gland However, melatonin secretion is more accurately regarded as a linked manifestation of the circadian rhythm than as its controlling mechanism The main cellular element of the gland, the pinealocyte, is thought to be derived from neural photoreceptors in lower vertebrates The latter cells, structurally analogous to retinal cones, transduce light directly into neural impulses and are among the mechanisms for circadian entrainment of hormonal rhythms In humans, the pineal no longer possesses the ability to transduce light directly However, it does retain an input from photic stimuli and in uences the circadian light-dark cycle through a pathway that originates in the retina, synapses in the suprachiasmatic nucleus, passes through descending sympathetic tracts to the intermediolateral cell columns and superior cervical ganglia, and then ascends to innervate noradrenergic terminals on the pinealocytes Darkness elicits a release of norepinephrine from the photoreceptors, stimulating the synthesis and release of melatonin During daylight the retinal photoreceptor cells are hyperpolarized, norepinephrine release is inhibited, and there is little melatonin production The concentration of the hormone peaks between 2 and 4 AM and gradually falls thereafter An approximate circadian rhythmicity to melatonin release is preserved in continuous darkness, and inexplicably, the blind maintain a light suppression of secretion It is readily appreciated that, in humans, it is dif cult to separate the changes that occur in the suprachiasmatic nucleus from those of the pineal Like other neuroendocrine cells, pinealocytes release peptides that are produced in the Golgi apparatus and packaged in secretory granules Whether secretion is the main mechanism for melatonin release is unclear, because these cells can utilize an alternative ependymal type of vacuolar secretion The entire gland is invested by a rich vasculature to receive the released peptide (in some mammals the blood ow per gram of pineal tissue is surpassed only by that of the kidney) The biochemistry and physiology of melatonin have been extensively reviewed by Brzezinski In humans, a regular feature of pineal pathology is the accumulation of calcareous deposits, commonly thought to be calcium but actually composed of carbonate-containing hydroxyapatite These concretions are formed within vacuoles of pinealocytes and released into the extracellular space This mineralization of the pineal body provides a convenient marker for its position in plain lms and on various imaging studies It is of signi cance that pineal tumors do not secrete melatonin, but the loss of melatonin may be used as a marker for the completeness of surgical pinealectomy Most interest in the past several years has centered around melatonin as a sopori c agent and its potential to reset sleep rhythms Its concentration in depressive illnesses, especially in the affected elderly, is also decreased
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